EpiPredict>Research>Projects>Identifying personalized epigenetic endocrine resistance based on pathway screening

Identifying personalized epigenetic endocrine resistance based on pathway screening

Simone Borgoni MSc

Early Stage Researcher 5
Name: Simone Borgoni
Gender: Male
Country of Birth: Italy
MSc in: Molecular biotechnology (University of Torino, IT)

Marie Skłodowska Curie PhD Fellowship in Molecular Biology/Biochemistry at the Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany, in the Division of Molecular Genome Analysis of Prof. Wiemann. The group aims to understand the complex molecular mechanisms that regulate signalling networks controlling cancer development, metastasis, and drug response as prerequisite to advance personalized treatment. Visit http://www.dkfz.de/en/mga to learn more about the group

Project title: “Identifying personalized epigenetic endocrine resistance based on pathway screening”
Supervisors: PI Prof Wiemann (DKFZ), EpiPredict co-PI Dr Olek (Epiontis)
PhD programme: DKFZ Helmholtz International Graduate School for Cancer Research (www.dkfz.de/en/phd-program) and Faculty of Biosciences, University Heidelberg, Germany

Key Objectives & Expected Results

Brief overview of this project’s objectives and expected results:

Objectives

To uncover pathway activities in clinical ER- positive tumor samples via systematic screening with Reverse Phase Protein Array (RPPA) technology towards stratification of molecular subtypes
To determine epigenetic/gene expression profiles (Illumina 450k and gene expression arrays/RNA-seq).
To identify gene mutations (DNA sequencing) in the same patients.
To correlate patients’ pathway activation, epigenetic/expression and mutation profiles with clinical annotation (time to relapse/time to recurrence)
To correlate clinical pathway activation profiles with equivalent profiles in resistance-induced cell line models.

Expected Results

Quantitative time-resolved perturbation data by in vitro experimentation that will serve as a basis to model drug response mechanisms.
Insights which signalling pathways are affected in epigenetically subclassified patients
Prediction of mechanisms leading to drug resistance, metastasis formation
Experimental validation of mechanisms by means of perturbation experiments (RNAi, CRISPR, etc.)

Host training: ChIP-seq, gene expression (Ilmunina), Bisufite-450k, Patient tissue, sera, cell lysates, RPPA pathway activation screening, next generation sequencing

Planned secondment(s): Epiontis: DNA methylation kit development (M29-30), UvA: Bioinformatics/modelling (M12-13), ), MTA-SZBK: DNA methylation interference tools (M19)